Safe use of selected cephalosporins in penicillin-allergic patients: a meta-analysis

Recent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to a cephalosporin in penicillin-allergic patients is smaller than previously postulated.

Medline and EMBASE databases were searched with the keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 through 2005. Among 219 articles retrieved, 9 served as source material for this evidence-based meta-analysis.

A significant increase in allergic reactions to cephalothin (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.1 to 5.5), cephaloridine (OR = 8.7; CI = 5.9 to 12.8), and cephalexin (OR = 5.8; CI = 3.6 to 9.2), and all first generation cephalosporins plus cefamandole (OR = 4.8; CI = 3.7 to 6.2) were observed in penicillin allergic patients; no increase was observed with second generation cephalosporins (OR = 1.1; CI, 0.6 to 2.1) or third generation cephalosporins (OR = 0.5; CI = 0.2 to 1.1). Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins.

First-generation cephalosporins have cross-allergy with penicillins, but cross-allergy is negligible with second- and third-generation cephalosporins. Particular emphasis should be placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents.